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United States Patent |
5,514,681
|
Wren
|
May 7, 1996
|
Compositions and methods for controlling pest insects
Abstract
Compositions of a purine, a xanthine oxidase inhibitor and/or a
dihydrofolate reductase inhibitor, and methods of using same, for
controlling the growth of pest insects which salvage, store, or excrete
their nitrogenous wastes via the purine metabolic pathway.
Inventors:
|
Wren; Heather N. (New Castle, VA)
|
Assignee:
|
Virginia Tech Intellectual Properties, Inc. (Blacksburg, VA)
|
Appl. No.:
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291072 |
Filed:
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August 17, 1994 |
Current U.S. Class: |
514/263.3; 424/84 |
Intern'l Class: |
A01N 043/54; A01N 043/90 |
Field of Search: |
514/262,263,264,258
424/84
|
References Cited
U.S. Patent Documents
4857532 | Aug., 1989 | Koehler et al. | 514/262.
|
4883801 | Nov., 1989 | Nathanson | 514/263.
|
4902690 | Feb., 1990 | Nathanson | 514/213.
|
Other References
Wren, "Tem Evidence of Urocytes in the Cockroach Fat Body", Tissue and Cell
23(2):291-292 (1991).
Mullins et al., "Maternal and Paternal Nitrogen Investment in Blattella
germanica (L.) (Dictyoptera; Blattellidae)", J. exp. Biol. 162:55-72
(1992).
Engebretson & Mullins, "Effects of a Purine Inhibitor, Allopurinl, on Urate
Metabolism in the German Cockroach, Blattella germanica L. (Dictyoptera:
Blattellidae)S", Comp. Biochem. Physiol. 83B(1):93-97 (1986).
Suiter et al., "Dietary Effects of Allopurinl and Sulfinpyrazone on
Development, Survival, and Reproduction of German Cockroaches
(Dictyoptera: Blattellidae)", J. Econ. Entomol. 85(1):117-122 (1992).
Wren & Cochran, "Xanthine Dehydrogenase Activity in the Cockroach
Endosymbiont Blattabacterium cuenoti (Mercier 1906) Hollande and Favre
1931 and in the Cockroach Fat Body", Comp. Biochem, Physiol.
88B(3):1023-1026 (1987).
Cruden & Markovetz, "Microbial Ecology of the Cockroach Gut", Ann. Rev.
Microbiol. 41:617-643 (1987).
Suiter et al., "Age-and Sex-Related Effects in German Cockroaches Fed an
Allopurinol Diet (Dictyoptera: Blattellidae)", J. Med. Entomol.
30(5):907-912 (1993).
Cochran: "Feeding, Drinking and Urate Excretory Cycles in Reproducing
Female Parcoblatta Cockroaches", Comp. Biochem. Physiol. 84A(4):677-682
(1986).
Wigglesworth, "Histochemical Studies of Uric Acid in Some Insects. I.
Storage in the Fat Body of Periplaneta americana and the Action of the
Symbiotic Bacteria", Tissue and Cell 19(1):83-91 (1987).
Cochran, "Comparative Analysis of Excreta from Twenty Cockroach Species",
Comp Biochem. Physiol. 46A:409-419 (1973).
Mullins & Cochran, "Nitrogen Excretion in Cockroaches: Uric Acid is Not a
Major Product", Science 177:699-701 (1972).
Massey et al., "On the Mechanism of Inactivation of Xanthine Oxidase by
Allopurinl and Other Pyrazolo 3,4-d!pyrimidines", J. Biol. Chem.
245(11):2837-2844 (1970).
Slansky, "Xanthine Toxicity to Caterpillars Synergized by Allopurinl, a
Xanthine Dehydrogenase/Oxidase Inhibitor", J. Chem. Ecol. 19(11):2635-2650
(1993).
|
Primary Examiner: Robinson; Allen J.
Attorney, Agent or Firm: Pennie & Edmonds
Claims
We claim:
1. A composition for controlling an insect pest which salvages, stores, or
excretes its nitrogenous wastes via the purine metabolic pathway,
comprising a purine selected from the group consisting of xanthine,
hypoxanthine and mixtures thereof, in amount of about 1% by weight, and
oxypurinol, in an amount of about 0.1% to about 3.0% by weight.
2. A composition according to claim 1, wherein the amount of oxypurinol is
about 0.1% by weight.
3. A composition according to claim 1, wherein the amount of oxypurinol is
about 0.5% by weight.
4. A composition according to claim 1, wherein the amount of oxypurinol is
about 1.0% by weight.
5. A composition according to claim 1, wherein the amount of oxypurinol is
about 2.0% by weight.
6. A composition according to claim 1, wherein the amount of oxypurinol is
about 3.0% by weight.
7. A method of controlling an insect pest which salvages, stores, or
excretes its nitrogenous wastes via the purine metabolic pathway, which
comprises bringing into contact with said pest, a growth-controlling
amount of a composition comprising a purine selected from the group
consisting of xanthine, hypoxanthine and mixtures thereof, in an amount of
about 1% by weight, and oxypurinol, in an amount of about 0.1% to about
3.0% by weight.
8. A method according to claim 7, wherein the insect is a cockroach.
9. A method according to claim 7, wherein the purine is xanthine.
10. A method according to claim 7, wherein the purine is hypoxanthine.
11. The method according to claim 7, wherein said composition is
administered by incorporation into a bait or attractant for pest insects
which is ingested by said pest insects.
12. A method according to claim 7, wherein the amount of oxypurinol is
about 0.1% by weight.
13. A method according to claim 7, wherein the amount of oxypurinol is
about 0.5% by weight.
14. A method according to claim 7, wherein the amount of oxypurinol is
about 1.0% by weight.
15. A method according to claim 7, wherein the amount of oxypurinol is
about 2.0% by weight.
16. A method according to claim 7, wherein the amount of oxypurinol is
about 3.0% by weight.
Description
BACKGROUND OF INVENTION
1. Field of the Invention
The present invention is directed to the regulation of the growth of pest
insects which utilize the purine metabolic pathway to salvage, store, or
excrete their nitrogenous wastes. It comprises bringing into contact with
the pest insects, formulations containing growth-controlling amounts of
compositions comprising purines, purine metabolic-enzyme inhibitors, and
inhibitors of enzymes which regulate production of specific co-factors of
this pathway.
2. Description of the Background Art
Despite the recent development and great promise of such advanced
insect-controlling techniques as chemical sterilants, pheromones, and
ecologically-based control strategies, the use of chemical insecticides
still plays a predominant role. However, rising public awareness of
environmental issues, more stringent government regulations, and
increasing insect resistance to conventional modalities are driving the
pest control industry to seek safer alternatives to these conventional
chemical insecticides.
Others have attempted to identify and evaluate the efficacy of insect
growth inhibitors. However, given the continuous need for increased
selectivity and effectiveness of insect control agents, it became
desirable to engage in rational formulation of control agents based on an
understanding of key insect nutritional and metabolic pathways.
SUMMARY OF THE INVENTION
It is widely acknowledged that the majority of insects are uricotelic in
that they excrete their excess nitrogen as uric acid and uricolytic
derivatives thereof (Cochran (1975), "Excretion in Insects" in Insect
Biochemistry and Function pp. 171-281). The uric acid is synthesized, via
the purine catabolic pathway shown in FIG. 1, and is either excreted to
the outside, or, in some cases, stored by the insect as a metabolic
reserve.
Cockroaches are a good model of the essential nature of storage-excretion
of uric acid. For example, in German cockroaches, a slurry of uric acid is
passed to the female during mating, as a paternal investment. The female,
in turn, invests the developing eggs with a supply of uric acid that is
used during embryogenesis (Mullins and Keil (1980), Nature 283: 567-569).
Interruption of this vital cycle appears highly detrimental to cockroach
population growth, which depends heavily on these uric acid stores
(Engebretson and Mullins (1986), Comp. Biochem. Physiol. 83B: 93-97;
Suiter et al. (1992), J. Econ. Entomol. 85(1): 117-122). In the cockroach
fat body, de novo synthesis of uric acid takes place, largely through
purine salvage, in the trophocytes and the uric acid is stored in
specialized urocytes for recycling (Cochran (1985), Ann. Rev. Entomol. 30:
29-49). This is accomplished through uricolytic digestion of the stored
urates by endosymbiont bacteria which are sequestered in bacteriocyte
cells adjacent to the urocytes (Wren and Cochran (1987), Comp. Biochem.
Physiol. 88B: 1023-1026). In this part of the uric acid cycle, the
endosymbiont bacteria use xanthine dehydrogenase to reduce the urates to
xanthine, and disruption of any part of this system also inhibits
population growth.
Another essential facet of insect physiology is the molt cycle, when the
cuticular epithelial cells multiply and synthesize a new, larger
exoskeleton just prior to ecdysis (Chapman (1982), The Insects Structure
and Function. Cambridge, Mass.: Harvard University Press, Hepburn (1985),
"The Integument" in Fundamentals of Insect Physiology. Ed. M. S. Blum, pp.
139-183. New York: John Wiley and Sons, Inc.). At the same time, many of
the internal tissues are growing, as in cockroaches where, for example,
development of the internal and external reproductive organs progresses
with each stage, culminating at the final molt to the sexually mature
adult (Chapman (1982) The Insects Structure and Function, Cambridge Mass.:
Harvard University Press). During this process, insects draw heavily on
their metabolic reserves to achieve the rapid growth of cells which takes
place.
The purine metabolic pathway is central to all of these processes, and,
thus, to homeostasis of insects. As in any of the known biochemical
pathways, the hydrolytic enzymes and their co-factors are essential to the
functioning of the purine degradative pathway. This pathway also serves to
salvage the free purine bases for re-use in nucleotide and nucleic acid
biosynthesis (Lehninger (1970) Biochemistry: The Molecular Basis of Cell
Structure and Function. 2nd Ed. pp. 740-742).
Two of the enzymes involved in this pathway are xanthine oxidase and
dihydrofolate reductase (also known as tetrahydrofolate dehydrogenase).
Xanthine oxidase (E. C. 1.2.3.2), a molybdenum iron sulfur flavo-enzyme,
functions late in the salvage pathway of purine catabolism from guanosine
monophosphate and inosine monophosphate to xanthine, and finally, to uric
acid. In this pathway, xanthine oxidase catalyzes both the conversion of
hypoxanthine to xanthine, and the conversion of xanthine to uric acid
(Coughlan (1980) Molybdenum and Molybdenum-Containing Enzymes. New York:
Pergamon Press). Functioning as xanthine dehydrogenase, the same enzyme
reduces uric acid to xanthine in the uricolytic pathway of the
endosymbiont bacteria in the cockroach fat body (Wren and Cochran (1987),
Comp. Biochem. Physiol. 88B: 1023-1026). Dihydrofolate reductase catalyzes
the synthesis of tetrahydrofolate, which is an essential co-factor in the
uric acid and purine synthesis pathways (Kucers and Bennett (1979),
"Trimethoprim and Cotrimoxazole" in The Use of Antibiotics. 3rd Ed.
London: William Heinemann Medical Books, Ltd.).
An understanding of these insect systems, which rely on the recycling and
excretion of their purines, led to the present invention, which provides
novel compositions and methods for disrupting insect homeostasis and
inhibiting insect population growth. Thus, in one embodiment, these
compositions comprise (1) a purine such as guanine
(2-amino-1,7-dihydro-6H-purin-6-one); hypoxanthine
(1,7-dihydro-6H-purin-6-one); or xanthine
(3,7-dihydro-1H-purine-2,6-dione), and mixtures thereof, and (2) a
xanthine oxidase inhibitor, preferably one of the 6-unsubstituted
pyrazolo 3,4-d!pyrimidine group, such as oxypurinol (4,6-dihydroxypyrazolo
3,4-d!pyrimidine); 4-mercapto-6-hydroxypyrazolo 3,4-d!pyrimidine;
4,6-dimercaptopyrazolo 3,4-d!pyrimidine,
4-amino-6-hydroxypyrazolo 3,4-d!pyrimidine;
4-hydroxy-6-mercapto 3,4-d!pyrimidine; or allopurinol
(4-hydroxypyrazolo 3,4-d!pyrimidine), and mixtures thereof. In another
embodiment, these compositions comprise (1) a purine; (2) a xanthine
oxidase inhibitor; and (3) a dihydrofolate reductase inhibitor such as
trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine),
methotrexate
(N- 4- (2,4-diamino-6-pteridinyl)methyl!methylamino!benzoyl!-L-glutamic
acid), or pyrimethamine
(5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine), and mixtures thereof.
While specific purines in combination with specific enzyme inhibitors are
utilized to illustrate the present invention, it is understood that any of
the purines and inhibitors of any of the enzymes of the pathway of FIG. 1
may be applied according to the present invention.
Furthermore, while the cockroach is utilized to illustrate the present
invention, it is understood that the compositions and methods of the
present invention may be applied to regulate the growth of any pest insect
which utilizes the purine metabolic pathway to salvage, store, or excrete
to the outside, its nitrogen wastes.
A further embodiment of the invention comprises an insect bait or
attractant formulation containing an insect-growth-regulating effective
amount of the compositions.
DESCRIPTION OF THE FIGURES
FIG. 1 shows the pathway for purine catabolism.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is predicated on the discovery that ingestion of
formulations containing growth controlling amounts of certain novel
compositions by pest insects, particularly cockroaches, disrupts
homeostasis and inhibits population growth.
The compositions of the present invention may be the sole active
ingredients of the formulation or they may be admixed with one or more
additional active ingredients, such as other, conventional insecticides.
The compositions of the present invention may be formulated with a "bait"
or "attractant." For purposes of description of the present invention,
these terms refer to any formulation to which pest insects are attracted
and which they will ingest. Such compositions are well-known to those
skilled in the art and it will be understood that any such material which
is inert with respect to the compositions of the present invention may be
employed in the practice of the invention.
In use, the formulations may be applied to the pest insects, to the locus
of the pest insects, and/or to the habitat of the pest insects.
The following examples are included for purposes of illustration only and
are not intended to be limiting, unless otherwise specified.
EXAMPLE 1
General Procedure
German cockroaches (Blatella germanica L.) from the stock laboratory "VPI"
strain were used to form experimental colonies of mixed life stages.
Unless otherwise specified, each insect colony of 42 insects contained
five each of newly post-emergent adult males and females, eight each of
male and female nymphs at the fifth nymphal stage, and eight each of male
and female nymphs at the third nymphal stage. Care was taken to select
insects from the same stock colonies for each experimental block, and each
colony was allowed to acclimatize for twenty-four (24) hours prior to
treatment.
The colonies were housed in one-gallon glass battery jars fitted with
fiber-board platforms, with clean tap-water offered continuously in
cotton-stoppered glass vials. The jars were rimmed with a thin coating of
petrolatum, and covered closely with three layers of cheesecloth held in
place with strong elastic bands. These measures prevented escape of the
test insects, as well as contamination by other insects.
Each test included "control" colonies, in which the food was untreated, and
"test" colonies, in which the food was mixed with the compositions being
tested to form percent concentrations by weight (w/w). Unless otherwise
specified, the food was Agway Laboratory Rat Chow and was prepared by
grinding the chow pellets to a fine powder and, for test colonies,
incorporating the test compounds by grinding and mixing them with the
chow, using a mortar and pestle. Food, either treated or untreated, was
pre-weighed in stainless steel planchettes and offered with the
planchettes placed in plastic cups, to avoid loss through spillage. During
tests, the planchettes were weighed weekly and food replenished when
necessary.
Replicate colonies were initiated on consecutive days, with all colonies
housed in the stock laboratory under the same conditions of ambient
temperature (25.degree. C.), and humidity as during rearing. A control
"blank colony", which was identical to a control colony except that no
insects were included, was monitored for loss or gain of moisture in the
food due to changes in ambient humidity. Any such changes were factored
into the calculations of food consumption.
A record was kept of all dead insects, which were counted and sexed weekly
when the food was weighed. Dead insects were frozen and stored at
-4.degree. C. prior to being subjected to a whole-body uric acid assay.
Unless otherwise specified, the total population of each colony was
counted every three (3) weeks. When all of the insects, or all of the
females, were dead or moribund, the colony was determined to be non-viable
and the experiment was terminated. Remaining insects were killed by
freezing and stored frozen, as above, to await assaying for uric acid.
The mean percent change (.DELTA.%) in population number for each colony was
calculated, with the initial number (42) representing 100%. Food
consumption, in milligrams per individual cockroach (ICmg), was calculated
for the first three (3) weeks of the experiment, prior to nymphs hatching.
These measurements determined whether the test compositions were ingested,
and whether such compositions were effective in inhibiting population
growth.
EXAMPLE 2
Uric Acid Assay
Determination of the whole-body uric acid content of the dead cockroaches
was conducted essentially according to a standard uricase assay (Cochran
(1973) Comp. Biochem. Physiol. A46: 409-419). Individual cockroaches, with
wings and legs trimmed off, were dried for 24-48 hours at 60.degree. C.
weighed and ground to a fine powder. Uric acid was extracted from the dry
tissue with 0.6% aqueous lithium carbonate for three (3) hours at
60.degree. C. with continuous shaking. The extracts were centrifuged to
remove tissue debris. After mixing with uricase, the maximum absorption at
292 nm was determined spectrophotometrically, and uric acid concentration
was calculated in .mu.g uric acid/mg of dry tissue.
EXAMPLE 3
Assessment of Xanthine Food Compositions
In two experiments (3a) and (3b), the effects of adding 1% xanthine Sigma
Chemical Co.! to the basic cockroach diet of ground rat chow, were
studied. The colonies in each experiment were set up as described in
Example I, with the diets being either rat chow alone (RC), or rat chow+1%
xanthine (RCX). Each experiment included three replicate colonies for each
condition (n=3).
The populations were counted at 6 and 9 weeks (3a) or 10 and 12 weeks (3b),
and the percent change in mean population numbers (.DELTA.%) was
calculated. Individual consumption (ICmg) of the diets for the first three
weeks of treatment was calculated from the food-weight data.
The results are shown in Table 1. The addition of xanthine appeared neither
to inhibit feeding nor to adversely affect population growth. In fact,
xanthine appeared to enhance reproduction, as population numbers were
higher in xanthine-treated colonies than in those fed rat chow alone.
TABLE 1
__________________________________________________________________________
EXPERIMENT 3a EXPERIMENT 3b
ICmg ICmg
TIME
(.+-.SEM)
.DELTA. %(*)
(.+-.SEM)
.DELTA. %
(wk)
RC RCX RC RCX RC RCX RC RCX
__________________________________________________________________________
3 55.8
55.3 58.0
57.9
(.+-.0.9)
(.+-.2.7) (.+-.0.4)
(.+-.0.8)
6 +224%
+278%
9 +707%
+921%
10 +1405%
+1433%
12 +1774%
+1869%
__________________________________________________________________________
(*) + = increase
Mean individual consumption (IC mg) and percent change (.DELTA. %) in mea
population number over time (weeks), in colonies of German cockroaches
administered offered food without (RC) or with 1% xanthine (RCX). n = 3
EXAMPLE 4
Assessment of Xanthine-Oxypurinol Compositions
Colonies of German cockroaches were prepared as described. The diets
administered were rat chow alone (RC); rat chow with oxypurinol Sigma
Chemical Co.! (RC+OXY %); and rat chow with 1% xanthine (RCX) and with
oxypurinol (+OXY %) at five concentrations (w/w). Individual consumption
(ICmg), population growth control, and whole-body uric acid concentrations
were determined.
Individual consumption (ICmg) in the first three weeks was calculated, and
the results shown in Table 2a below. The addition of oxypurinol alone
caused a decrease in food consumption over controls fed untreated food.
The addition of xanthine to the diet caused the consumption of
oxypurinol-treated food to increase by 35% at 0.1% oxypurinol
concentration, and by 56% at the 1.0% oxypurinol concentration.
TABLE 2a
__________________________________________________________________________
XANTHINE 0% XANTHINE 1%
TIME RC + OXY %
RC + OXY %
(wk)
RC 0.1 1.0 0.1 0.5 1.0 2.0 3.0
__________________________________________________________________________
3 53.7 36 32 48.5
58.3
49.9 52.6
45.6
(.+-.2.0)
n =1
n = 1
(.+-.1.4)
(.+-.0.8)
(.+-.1.9)
(.+-.1.5)
n = 1
n = 9* n = 6
n = 3
n = 6
n = 6
__________________________________________________________________________
*n = number of columns
Mean individual consumption (IC mg) of rat chow over three weeks, with or
without 1% xanthine, and with various concentrations (w/w) of oxypurinol
(OXY %).
The percent change (.DELTA.%) in mean colony population numbers at 5.5, 6,
7, 9, 10 and 12 weeks of treatment were determined as described, with the
results shown in Table 2b below. The addition of oxypurinol alone to the
diet did not inhibit population growth. The addition of xanthine plus
oxypurinol inhibited population growth to the point of extinction.
TABLE 2b
__________________________________________________________________________
XANTHINE 0% XANTHINE 1%
TIME
RC RC + OXY %
RC + OXY %
(wk)
CONTROL
0.1 1.0 0.1 0.5 1.0 2.0 3.0
__________________________________________________________________________
5.5
+690% +460%
+1060%
n = 1 n = 1
n = 1
6 +126% -31%
-50%
-5% -11% -55%
n = 5
9 +812% -92%
-92%
-64% -77% -88%
n = 5
7 +719% -64% -75% -69%
10 +405% -91% -98% -98%
12 +1774% -94% -100%
-100%
__________________________________________________________________________
Percent changes (+ or - .DELTA. %) in mean population number, in colonies
of German cockroaches offered food with or without 1% xanthine, and with
various concentrations (w/w) of oxypurinol (OXY %), over time (weeks).
Except where noted, n = 3.
Whole-body uric acid concentrations were calculated from standard uricase
assays for cockroaches that died during weeks 5-9 of treatment. Samples
from the VPI laboratory strain of German cockroaches also were assayed to
show typical "base-line" levels of urates before treatment.
As shown in Table 2c below, females in the VPI strain typically exhibit a
slightly higher uric acid level than males, regardless of stage. However,
as shown in Tables 2d-2f below, after several weeks of feeding with
xanthine and oxypurinol in the diet, there is a marked decline in
whole-body urate concentration in all groups regardless of age or sex.
TABLE 2c
______________________________________
AGE URIC ACID
STAGE GENDER (wks) .mu.g/mg .+-. SEM
______________________________________
adult males 6-7 1.80 .+-.
n = 9 0.12
females 2.41 .+-.
n = 10 0.06
nymph males 5-6 2.34 .+-.
n = 10 0.10
females 2.44 .+-.
n = 10 0.22
nymph males 3-4 0.77 .+-.
n = 10 0.10
females 1.51 .+-.
n = 10 0.10
______________________________________
Mean, wholebody uric acid concentrations (.mu.g/mg of dry tissue weight,
.+-. SEM), in different age and gender groups of the VPI laboratory strai
of German cockroaches that are typical of those used in the feeding
experiments.
TABLE 2d
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0
______________________________________
5 2.42 .+-. 0.54 .+-. 0.32 .+-.
0.31 .+-.
0.12 0.05 0.06 0.05
n = 5 n = 25 n = 17 n = 17
6 2.79 .+-. 0.43 .+-. 0.30 .+-.
0.27 .+-.
0.21 0.04 0.04 0.03
n = 4 n = 32 n = 35 n = 26
7 2.78 .+-. 0.54 .+-. 0.25 .+-.
0.21 .+-.
0.25 0.10 0.04 0.04
n = 6 n = 8 n = 14 n = 12
9 3.16 .+-. 0.51 0.14 .+-.
0.32 .+-.
0.06 n = 1 0.04 0.10
n = 10 n = 7 n = 3
______________________________________
Mean wholebody uric acid concentrations (.mu.g/mg dry tissue weight .+-.
SEM) in male German cockroaches on food without (RC), or with 1% xanthine
(RCX) and various percent concentrations (w/w) of oxypurinol (OXY %).
TABLE 2e
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0
______________________________________
5 2.63 .+-. 0.31 .+-. 0.31 .+-.
0.28 .+-.
0.14 0.13 0.04 0.08
n = 3 n = 6 n = 8 n = 7
6 3.13 .+-. 0.31 .+-. 0.34 .+-.
0.35 .+-.
0.04 0.03 0.06 0.06
n = 4 n = 27 n = 27 n = 18
7 2.95 .+-. 0.43 .+-. 0.22 .+-.
0.26 .+-.
0.18 0.04 0.04 0.06
n = 4 n = 24 n = 23 n = 14
9 3.14 0.21 .+-. 0.29 .+-.
0.34 .+-.
n = 1 0.03 0.04 0.05
n = 21 n = 14 n = 13
______________________________________
Mean wholebody uric acid concentrations (.mu.g/mg dry tissue weight .+-.
SEM) in female German cockroaches on food without (RC), or with 1%
xanthine (RCX) and various percent concentrations (w/w) of oxypurinol
(OXY).
TABLE 2f
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0
______________________________________
5 1.95 .+-. 0.53 .+-. 0.32 .+-.
0.36 0.04 0.18
n = 4 n = 3 n = 2
6 2.95 .+-. 0.08 .+-.
0.09 0.06
n = 5 n = 2
7 3.14 .+-. 0.13 .+-.
0.03 0.08
n = 4 n = 2
9 3.26 0.14
n = 1 n = 1
______________________________________
Mean wholebody uric acid concentrations (.mu.g/mg dry tissue weight .+-.
SEM) in German cockroach nymphs offered food without (RC), or with 1%
xanthine (RCX) and various percent concentrations (w/w) of oxypurinol
(OXY).
EXAMPLE 5
Assessment of Xanthine-Oxypurinol Compositions Offered for Different
Durations
Colonies were prepared as described. The food was treated with 1% xanthine
and various concentrations of oxypurinol, and was offered for durations of
either 24 hours, or 1, 2, or 3 weeks. At the end of the treatment time,
the treated food was removed, and the insects were offered untreated rat
chow for the remainder of the test time.
As shown in Table 3 below, the data indicates that a minimum dose of
oxypurinol must be ingested over time to achieve population inhibition.
For example, the 24-hour treatment affected population numbers when
compared with the control, but did not control population numbers at any
concentration of oxypurinol. Calculation revealed that the individual
consumption of oxypurinol ingested during this time ranged from 6-104
.mu.g.
TABLE 3
__________________________________________________________________________
TREATMENT
TIME RCX + OXY %
DURATION (wks)
RC 0.1 1.0 2.0
__________________________________________________________________________
24 hours 6 +500% +250% +114% +109%
1 week 6 +887% +137% -45% -49%
9 +1157%
+320% -63% -57%
12 +1580%
+853% -5% -31%
2 weeks 9 +591% +36% -65% -90%
12 +750% +213% -66% -94%
15 >+750% +561% -45% -96%
3 weeks 6 +391% -58% -71% -92%
9 +1050%
-71% -92% -97%
12 +1604%
-79% -96% -98%
__________________________________________________________________________
Percent change (+ or -) in mean population numbers in colonies fed a diet
of rat chow alone (RC), or rat chow combined with 1% xanthine (RCX), and
with various concentrations (w/w) of oxypurinol (OXY %). Duration of
treatments was 24 hrs, or 1, 2, or 3 weeks, after which rat chow alone wa
offered. n = 3.
Treatment with 0.1% oxypurinol for one or two weeks also resulted in lower
population numbers when compared with controls, and delayed egg-hatch by
1-2 weeks, but the treated colonies were recovering when they were
terminated at 12 weeks. However, three (3) weeks of treatment at 0.1%
oxypurinol did cause a substantial reduction in population numbers in the
weeks following treatment, with no recovery noted by 12 weeks, and with
only one viable eggcase, which hatched six weeks later than normal.
Colonies treated for two (2) weeks with 2% oxypurinol, or for three (3)
weeks with 1% or 2% oxypurinol did not recover, even when the "recovery"
time was extended to fifteen (15) weeks. Mean individual consumption of
oxypurinol was 734 .mu.g, 579 .mu.g, and 1,140 .mu.g respectively.
EXAMPLE 6
Assessment of Food Choice
Colonies were prepared as described, with three replicates of each
condition. Planchettes containing either untreated food (RC) or food
treated with xanthine+oxypurinol (RCX+0%) were offered together in each
colony. Food weights for each planchette were calculated to determine how
much of each was consumed. The treatments consisted of rat chow with 1%
xanthine and oxypurinol at either 0.1%, 0.5% or 1.0% (w/w) concentration.
The control colony was given two planchettes of untreated rat chow.
The results, as shown in Table 4 below, indicate that the insects consumed
either the same quantity of treated and untreated food (at 0.5%
oxypurinol), or ate more of the treated than the untreated food (at 0.1%
and 2.0% oxypurinol). The range of oxypurinol ingested was calculated to
be between 29 .mu.g and 265 .mu.g per individual over the first three
weeks, and a high level of population-growth control was achieved,
especially at 1.0% oxypurinol concentration.
TABLE 4
__________________________________________________________________________
TIME RC RCX + 0% RCX + 0% RCX + 0%
(wks)
TEST CONTROL
RC 0.1 RC 0.5 RC 1.0
__________________________________________________________________________
3 IC mg .+-.
58.9 .+-.
23.1 .+-.
29.4 .+-.
25.7.+-.
25.6 .+-.
24.7.+-.
26.5
SEM 1.7 3.1 0.3 1.0 1.3 0.9 2.0
IC .mu.g
0 0 29.4 0 128 0 265
OXY
% TOTAL
100% 43% 57% 50% 50% 48% 52%
7 .DELTA. %
+422% -64% -72% -83%
9 .DELTA. %
+1378% -71% -80% -94%
12 .DELTA. %
+2007% -76% -71% -96%
__________________________________________________________________________
Individual consumption (IC mg) and percent change in mean population
numbers (.DELTA. %) over time (wks), in colonies where treated (RCX + 0%)
and untreated (RC) food were offered together as a choice of diet. The
amount of oxypurinol ingested over the first three weeks is shown as
.mu.g/individual (IC .mu.g OXY), and the ratio of treated and untreated
food consumed is given as a percent of the total amount eaten (% TOTAL).
EXAMPLE 7
Life Stage Effects of Xanthine-Oxypurinol Compositions
Colonies of German cockroaches were housed as previously described, with
the usually mixed stages separated into three different colonies. Colonies
consisted of either newly-molted adults (five males and five females, 6-7
weeks old); large nymphs (eight males and eight females, 5-6 weeks old);
or small nymphs (eight males and eight females, 3-4 weeks old). Colonies
of older adults (five males and five females, 7-8 weeks old) also were
tested.
Colonies were fed untreated rat chow (RC), or rat chow treated with 1%
xanthine (RCX) plus various levels (w/w) of oxypurinol (OXY %). Individual
consumption (ICmg) and percent change in mean population number (.DELTA.%)
were determined for each stage, and are shown in Tables 5a through 5d
below, for adults, large nymphs, small nymphs, and older adults,
respectively.
The data in these tables confirm that the primary impact of treatment with
xanthine plus oxypurinol occurs as the cockroaches attempt to reproduce.
The effect is probably caused by depletion of the insects' metabolic
reserves, including uric acid stores which cannot be replaced because of
irreversible enzyme inhibition. However, very small nymphs which hatch in
a dying colony also are affected in that they are usually too weak to
survive, and rarely reach their second instar. It is probable that they
are not invested with the metabolic reserves that are normally passed to
them prenatally. Their continued feeding on treated food also prevents the
young nymphs from developing their own metabolic stores, especially stores
of uric acid.
Adult males were observed to be the first to die. At mating, adult males
utilize a large part of their reserves to pass urates as well as mature
sperm to the females. Females who have just produced an egg-case, which
necessitates a large investment of nutritional reserves, die shortly
thereafter, usually with the non-viable egg-case protruding from the
ovipositor.
Cochran observed that cyclic feeding occurs in adult females in relation to
egg production (Cochran (1983) Entomol. Exp. Appl. 34: 51-57). In this
oothecal cycle, the females feed vigorously while maturing the oocytes,
and sparingly while carrying an egg-case. These phenomena would account
for the high feeding rates and early mortality of the newly-emerged adults
(Table 5a), as well as the low feeding rates of the older adults (Table
5d). These latter females were likely to already have matured the eggs
that would fill oothecae soon after the colony was assembled, and thus
were in the low feeding-rate part of their cycle. Their first nymphal
hatch would account for the precipitous rise in population numbers in
these colonies (Table 5d), followed by the gradual weakening of the
colonies as the adults attempted to reproduce further and the
newly-hatched nymphs died.
Nymphs followed the same pattern of mortality as the adults, and were most
affected by the treated diet after molting to the adult stage, when they
normally feed vigorously in preparation for maturing their first oocytes.
The delay in the rate at which the population declined in the large nymph
colony (Table 5b), and small nymph colony (Table 5c), is further evidence
that the major impact occurs during reproduction. This would have happened
between weeks 9-11 of the experiment for these age-groups.
The effective dosage range for oxypurinol with xanthine is very wide in
these experiments, causing high mortality at 99.5 .mu.g/individual
measured over three weeks in the newly-molted adults (Table 5a), and
slower control at higher individual consumption rates when the colonies
were started as nymphs. However, it is clear that, although there is a
different effect on the cockroaches depending on their age when treatment
is started, they are all affected as they attempt to reproduce.
TABLE 5a
______________________________________
COLONY STARTED AS ADULTS (n = 1)
TIME RCX + OXY %
wks TEST RC 0.1 1.0 2.0
______________________________________
3 IC mg 87.0 99.5 76.8 84.8
3 IC .mu.g OXY
0 99.5 768 1696
6 .DELTA. % +1430% -94% -75% -88%
9 .DELTA. % +1310% -100% -90% -100%
12 .DELTA. % +1810% -100% -100% -100%
______________________________________
Individual consumption (IC mg) and percent change in mean population
number (.DELTA. %) in colonies of newlymolted adult German cockroaches fe
untreated rat chow (RC) or rat chow treated with 1% xanthine (RCX) and
various concentrations (w/w) of oxypurinol (OXY %).
TABLE 5b
______________________________________
COLONY STARTED AS LARGE NYMPHS (n = 1)
TIME RCX + OXY %
wks TEST RC 0.1 1.0 2.0
______________________________________
3 IC mg 82.8 76.9 65.3 79.3
3 IC .mu.g OXY
0 76.9 653 1586
6 .DELTA. % -6% -50% -31% -6%
9 .DELTA. % +1613% -69% -81% -63%
12 .DELTA. % +1800% -88% -100% -100%
______________________________________
Individual consumption (IC mg) and percent change in mean population
number (.DELTA. %) in colonies of large German cockroach nymphs (5-6 week
old at the starting date) fed untreated rat chow (RC) or rat chow treated
with 1% xanthine (RCX) and various concentrations (w/w) of oxypurinol (OX
%).
TABLE 5c
______________________________________
COLONY STARTED AS SMALL NYMPHS (n = 1)
TIME RCX + OXY %
wks TEST RC 0.1 1.0 2.0
______________________________________
3 IC mg 54.9 53.9 52.4 40.4
3 IC .mu.g OXY
0 53.9 524 808
6 .DELTA. % -50% -31% -19% -81%
9 .DELTA. % +719% -69% -81% -88%
12 .DELTA. % +775% -88% -100% -100%
______________________________________
Individual consumption (IC mg) and percent change in mean population
number (.DELTA. %) of small German cockroach nymphs (3-4 weeks old at the
starting date) fed untreated rat chow (RC) or rat chow treated with 1%
xanthine (RCX) and various concentrations (w/w) of oxypurinol (OXY %).
TABLE 5d
______________________________________
COLONY STARTED AS OLDER ADULTS (n = 3)
TIME RCX + OXY %
wks TEST RC 0.1 1.0 2.0
______________________________________
3 IC mg .+-. 38.7 37.2 .+-.
35.0 .+-.
35.2 .+-.
SEM 1.9 0.6 1.8
3 IC .mu.g OXY
0 37.2 350 704
6 .DELTA. % +1150% +557% +403% +823%
9 .DELTA. % +1030% +33% +40% +197%
12 .DELTA. % +1820% -73% -67% -30%
______________________________________
Mean individual consumption (IC mg) and percent change in mean population
number (.DELTA. %) in colonies of older German cockroach adults (8-9 week
old at the starting date) fed untreated rat chow (RC) or rat chow treated
with 1% xanthine (RCX) and various concentrations (w/w) of oxypurinol (OX
%).
EXAMPLE 8
Assessment of Compositions Containing Trimethoprim
Replicate colonies of German cockroaches were prepared as described. The
diets administered were either rat chow alone (RC); rat chow with various
concentrations of trimethoprim (RC+T %) (w/w), or rat chow with 1%
xanthine (RCX) and various concentrations (w/w) of trimethoprim (T %).
As shown in Table 6a below, the addition of trimethoprim alone did not
inhibit population growth, although there was some eventual weakening of
the treated colonies. As shown in Table 6b below, however, the combination
of xanthine and trimethoprim caused rapid inhibition of population growth.
Whole-body uric acid concentrations were calculated from standard uricase
assays, as previously described. As shown in Table 6c below, uric acid
metabolism was not affected by treatment with a combination of xanthine
and trimethoprim.
During the first three-weeks, there was a mean .DELTA.% of -82% of the
populations in the treated colonies, with 65% of these still nymphs when
they died. This represents 72% of the nymphs used for the experiment, and
confirms that effects are most pronounced during nymphal molt.
TABLE 6a
______________________________________
TIME RCX + OXY %
wks TEST RC 0.1 1.0 2.0
______________________________________
3 IC mg .+-. 62 .+-. 61 .+-.
58 .+-.
54 .+-.
SEM 2.2 3.5 3.4 1.7
12 .DELTA. % +1398% +1246% +1013% +384%
______________________________________
Mean individual consumption (IC mg) of rat chow without (RC) or with
various concentrations (w/w) of trimethoprim (RC + T %). over time
(weeks), shown in conjunction with percent change in mean population
number (.DELTA. %), in colonies of German cockroaches where the starting
number (42) = 100%.
TABLE 6b
______________________________________
RCX + T %
TIME RC 1.0 2.0 3.0
wks TEST n = 6 n = 3 n = 12 n = 3
______________________________________
1 IC mg .+-.
17.3 .+-.
12.0 .+-.
8.8 .+-.
5.8 .+-.
SEM 2.4 0.9 0.7 0.1
.DELTA. % -1% -4% -28% -41%
3 IC mg .+-.
44.7 .+-.
33.9 .+-.
22.6 .+-.
13.4 .+-.
SEM 2.1 1.1 2.8 1.3
.DELTA. % -16% -23% -77% -98%
6 .DELTA. % +36% -44% -67% -98%
______________________________________
Mean individual consumption (IC mg), and percent change in mean populatio
number (.DELTA. %), over time (weeks), in colonies of German cockroaches
offered food without (RC), or with (RCX) 1% xanthine and various
concentrations (w/w) of trimethoprim (T %), where the colony starting
number (42) = 100%.
TABLE 6c
______________________________________
WEEK GROUP RC RCX + 2% T
______________________________________
3-4 males 2.04 .+-.
2.61 .+-.
0.12 0.05
n = 19 n = 9
females 2.54 .+-.
2.64 .+-.
0.06 0.03
n = 17 n = 3
nymphs 2.76 2.62 .+-.
n = 1 0.12
n = 9
______________________________________
Mean wholebody uric acid concentrations (.mu.g/mg dry tissue weight .+-.
SEM), in three groups of German cockroaches offered untreated food (RC),
or food treated with 1% xanthine (RCX) and 2% trimethoprim (w/w).
EXAMPLE 9
Treatment of Resistant Cockroaches with Xanthine-Oxypurinol Compositions
Colonies of cockroaches were prepared as previously described, except that
the insects were taken from laboratory stocks of two German cockroach
strains that are known to be resistant to insecticides commonly used for
cockroach control. The two strains were: (A) the Hawthorne strain, and (B)
the Las Palms strain. Profiles of the resistance ratios exhibited by these
two strains are shown in Table 7a below.
TABLE 7a
______________________________________
INSECTICIDE HAWTHORNE LAS PALMS
______________________________________
ORGANOPHOSPHATES
RR
Diazinon 2.0 >75
Chlorpyrifos 10.8 >50
Acephate 2.0 1.2
Malathion 5.5 >50
CARBAMATES
Propoxur 1.7 >60
Bendiocarb 2.2 >70
PYRETHROIDS
Pyrethrins >140 >140
Allethrin >140 >140
Permethrin 0.5 3.2
Phenothrin 0.6 >120
Fenvalerate 0.9 >60
Esfenvalerate 0.8 7.0
Cyfluthrin 1.8 2.5
Cypermethrin 1.6 >80
BIO-CHEMICAL
Avermectin 2.4 1.5
______________________________________
Resistance ratio (RR) profiles for the Hawthorne and Las Palms resistant
strains, where, on a continuum of rising resistance, RR >2.0 indicates
that resistance is developing, and RR .gtoreq.3.0 indicates that the gene
frequency for resistance has increased. RR is calculated as (Test strain
LT.sub.50) .div. (Susceptible strain LT.sub.50), where LT.sub.50 is the
time it takes for the intoxicant to achieve 50% mortality in a treated
population.
Individual consumption (ICmg) in the first three-weeks was calculated as
previously described. As shown in Tables 7b and 7c below, ICmg for both
strains was consistent across all concentrations of the food mixtures. The
Hawthorne strain exhibited a maximum decrease in consumption of 22% for a
diet containing 3% oxypurinol. This represents a dose of 1,260 .mu.g of
oxypurinol over the first three weeks.
TABLE 7b
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0 3.0
______________________________________
HAWTHORNE STRAIN
3 53.6 47.1 48.0 47.1 42.0
(.+-.3.5)
(.+-.0.6)
(.+-.1.3)
(.+-.0.8)
(.+-.0.4)
n = 4 n = 3 n = 3 n = 3 n = 4
LAS PALMS STRAIN
3 45.2 39.5 40.0 40.0 40.3
(.+-.1.3)
(.+-.1.0)
(.+-.0.4)
(.+-.2.3)
(.+-.0.5)
n = 4 n = 3 n = 3 n = 3 n = 4
______________________________________
Mean individual consumption (IC mg), over time (wks), of rodent chow
offered without (RC), or with 1% xanthine (RCX), and with various
concentrations (w/w) of oxypurinol (OXY %), by German cockroaches of the
Hawthorne and Las Palms resistant strains.
The effect of xanthine-oxypurinol combinations on population growth was
determined as previously described. As shown in Tables 7c and 7d below,
the combination controlled the population growth of both resistant
strains.
TABLE 7c
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0 3.0
______________________________________
6 +438% -32% -22% +12% -21%
9 +997% -55% -59% -38% -67%
12 +1,601% -77% -78% -76% -98%
______________________________________
Percent changes (+ or -) in mean population number in colonies of German
cockroaches of the Hawthorne resistant strain, offered food without (RC)
or with 1% xanthine (RCX), and with various concentrations (w/w) of
oxypurinol (OXY %), over time (weeks). n = 3.
TABLE 7d
______________________________________
TIME RCX + OXY %
(wks) RC 0.1 1.0 2.0 3.0
______________________________________
6 +146% -50% -68% +31% -25%
9 +1,074% -50% -8% -60% -70%
12 +1,624% -78% -67% -88% -95%
______________________________________
Percent changes (+ or -) in mean population number in colonies of German
cockroaches of the Las Palms resistant strain, offered food without (RC)
or with 1% xanthine (RCX), and with various concentrations (w/w) of
oxypurinol, over time (weeks). n = 3.
EXAMPLE 10
Treatment of Resistant Cockroaches with Xanthine-Trimethoprim Compositions
Colonies of cockroaches were prepared as described, using the Hawthorne and
Las Palms resistant strains.
As shown in Table 8a below, for the Hawthorne strain, feeding was inhibited
in relation to the control, in direct ratio to the concentration of
trimethoprim in the diet. The maximum decrease of 62% occurred at 4.0%T
concentration, which represents a dose of 639 .mu.g of trimethoprim per
individual over the first three weeks. Population growth of the Hawthorne
strain was controlled at the higher concentrations.
TABLE 8a
__________________________________________________________________________
TIME RCX + T %
(Wks)
TEST RC 0.5 1.0 2.0 3.0 4.0
__________________________________________________________________________
3 IC mg 42.5 37.6 37.1 30.4 17.2 15.9
(.+-. SEM)
(.+-.0.7)
(.+-.2.1)
(.+-.1.7)
(.+-.2.0)
(.+-.1.2)
(.+-.1.4)
n = 7
n = 3
n = 3
n = 6
n = 6
n = 3
3 .DELTA. %
-7% -2% -6% -27% -75% -79%
n = 7
n = 3
n = 3
n = 6
n = 4
n = 3
6 .DELTA. %
+368% -70% -79% -89%
n = 4 n = 3
n = 4
n = 3
9 .DELTA. %
+606%
+369%
+298%
-17% -95% -94%
n = 7
n = 3
n = 3
n = 6
n = 4
n = 3
12 .DELTA. %
+913% -51% -93% -97%
n = 3 n = 3
n = 3
n = 3
__________________________________________________________________________
Mean individual consumption (IC mg), and percent change (.DELTA. %) in
mean population numbers, in colonies of German cockroaches of the
Hawthorne resistant strain offered food without (RC), or with 1% xanthine
(RCX), and various concentrations (w/w) of trimethoprim (T %) over time
(weeks).
For the Las Palms strain, as shown in Table 8b below, an even decline in
ICmg of treated food occurred in direct relation to the increase in
concentration of trimethoprim. The maximum inhibition, compared with the
control, was 38% at 6%T concentration which constitutes an ingested dose
of 1,758 .mu.g of trimethoprim per individual over three weeks. Population
numbers were reduced by two-thirds at six weeks of treatment.
TABLE 8b
______________________________________
TIME RCX + T %
(wks) TEST RC 3.0 4.0 5.0 6.0
______________________________________
3 IC mg 47.0 43.0 41.3 37.0 29.3
(.+-. (.+-.3.8)
(.+-.3.5)
(.+-.2.2)
(.+-.2.3)
(.+-.1.8)
SEM)
3 .DELTA. %
-12% -24% -26% -43% -57%
6 .DELTA. %
+336% +100% -37% -37% -67%
______________________________________
Mean individual consumption (IC mg) and percent change (.DELTA. %) in mea
population number, in colonies of German cockroaches of the Las Palms
resistant strain offered food without (RC), or without 1% xanthine (RCX),
and with various concentrations (w/w) of trimethoprim (T%) over time
(weeks). n = 3
EXAMPLE 11
Treatment of Cockroaches with Xanthine-Oxypurinol-Trimethoprim Compositions
Colonies of German cockroaches of the VPI susceptible strain and colonies
of the Hawthorne resistant strain were offered either untreated rat chow
(RC), or rat chow treated (w/w) with 1% xanthine (RCX), combined with 2%
oxypurinol (OXY) and 2% trimethoprim (T). Individual consumption and
changes in colony populations results are shown in Tables 9a (VPI strain)
and 9b (Hawthorne strain). In both, colonies were virtually extinct by six
weeks of treatment, in spite of declines in ICmg of .gtoreq.50%.
TABLE 9a
______________________________________
TIME RC RCX + 2% OXY + 2% T
(wks) TEST n = 1 n = 3
______________________________________
3 IC mg 71.3 34.9
(.+-. SEM) (.+-.1.6)
3 .DELTA. % -5% -68%
6 .DELTA. % +955% -99%
______________________________________
Mean individual consumption (IC mg) and percent change (.DELTA. %) in mea
population number in colonies of German cockroaches of the VPI susceptibl
strain offered food without (RC), or with 1% xanthine (RCX) and with 2%
oxypurinol (OXY) and 2% trimethoprim (T) (w/w), over time (weeks).
TABLE 9b
______________________________________
TIME RC RCX + 2% OXY + 2% T
(wks) TEST n = 1 n = 3
______________________________________
3 IC mg 72 34.1
(.+-. SEM) (.+-.0.6)
3 .DELTA. % -2.4% -76%
6 .DELTA. % +1416% -98%
______________________________________
Mean individual consumption (IC mg), and percent change (.DELTA. %) in
mean population number in colonies of German cockroaches of the Hawthorne
resistant strain offered food without (RC), or with 14 xanthine (RCX) and
with 2% oxypurinol (OXY) and 2% trimethoprim (T) (w/w), over time (weeks)
EXAMPLE 12
Assessment of Purines with Oxypurinol or Trimethoprim
Colonies of cockroaches of the VPI susceptible strain were prepared as
previously described. The diets offered were rat chow alone (RC), rat chow
(w/w) with 1% xanthine and 3% trimethoprim (RCX+T), rat chow with 1%
hypoxanthine and 3% trimethoprim (HX+T), rat chow with 1% guanine and 3%
trimethoprim (G+T), and rat chow with 1% hypoxanthine and 1% oxypurinol
(HX+OXY). Individual consumption (ICmg), and change in population numbers
were calculated as before, with the results shown in Table 10, below.
The results, with hypoxanthine and guanine replacing the xanthine component
of the diet mixtures, compared closely with those obtained with xanthine.
This was the case with both trimethoprim and oxypurinol, with population
growth being controlled to extinction of the colonies. Some feeding
inhibition occurred in all of the trimethoprim mixtures.
TABLE 10
__________________________________________________________________________
TIME RC RCX + T
HX + T
G + T
HX + OXY
(wks)
TEST n = 2
n = 2 n = 2
n = 2
n = 1
__________________________________________________________________________
3 IC mg 54 26 25 29 42
(.+-. SEM)
(.+-.0)
(.+-.8.0)
(.+-.7.0)
(.+-.8.0)
3 .DELTA. %
-5.5 -68 -74 -71 -17
6 .DELTA. %
+152 -99 -91 -94 -83
9 .DELTA. %
+1426
-100 -100 -100 -100
__________________________________________________________________________
Mean individual consumption (IC mg), and percent change (.DELTA. %) in
mean population numbers, in colonies of German cockroaches of the VPI
susceptible strain offered food without (RC), or with 1% of a purine (w/w
and either 3% trimethoprim (T), or 1% oxypurinol (OXY), over time (weeks)
Purines were xanthine (X), hypoxanthine (HX), or guanine (G).
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